This program project will focus on the pathophysiology of the endothelial cell and its reactions in inflammation, thrombosis and atherosclerosis. Project 1 will examine platelet-endothelial interactions in culture, using biochemical and morphologic techniques. It will study mechanisms underlying thromboresistance of normal endothelium, endothelial injury caused by platelet products, and the effect of products of each cell on the other. Project 2 will study the role of molecular charge in endothelial permeability by examining the ultrastructural and biochemical distribution of differently charged molecular tracers in the microcirculation, in the aorta and in endothelial cultures. The objective of Project 3 is to study the mechanisms of endothelial proliferation in inflammation by examining the ability of inflammatory cells (macrophages, lymphocytes) to induce neovascularization in the cornea, and injury, proliferation or altered function of endothelial cells in culture. Project 4 will use a model of balloon injury to the aorta to study the interactions of platelets, lipids, and injured and regenerating endothelium and smooth muscle in the development of the atheromatous plaque. A tissue culture core will provide a continuous supply of endothelial cells, smooth muscle and other cell types for comparative studies, as well as develop new techniques for isolation and culture of microvascular endothelium. Morphologic techniques will include transmission and scanning electron microscopy, ultrastructural cytochemistry, autoradiography, and vascular tracer procedures.